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Extracellular potentials related to intracellular action potentials during impulse conduction in anisotropic canine cardiac muscle.

This paper considers a quantitative description of intracellular and transmembrane currents in anisotropic muscle, with emphasis on the factors that determine the extracellular potentials. Although Vmax of the intracellular action potential had no relation to changes in conduction velocity in anisotropic tissue with constant membrane properties, the extracellular waveforms were quite sensitive to velocity changes. Large amplitude biphasic deflection occurred in the fast areas, and in the slow areas the waveforms were of lower amplitude and triphasic in shape; i.e., negative potentials preceded the biphasic positive-negative deflection. The extracellular potentials were simulated on the bases of a model of intracellular currents, and the theoretical and measured results showed good agreement. In tissue with anisotropic conductivity, the relationship between the spatial intracellualr potential gradient and the magnitude of the extracellular potential of the excitation wave was opposite to the classical relationship in isotropic tissue. Due to the influence of the effective intracellular conductivity on the spread of intracellular currents and on conduction velocity, in anisotropic tissue the extracellular potential decreased as the intracellular potential gradient increased. The peak values of the positive and negative potentials and the spatial distribution of the potential gradients varied considerably along the activation front. These findings were accounted for by differences in the distribution and spatial extent of the transmembrane currents, which were determined by the intracellular currents. The theoretical analysis showed that intracellular and transmembrane currents were proportional to the local conduction velocities of the wavefront. Thereby, it was not possible to have a "uniform layer" of current when there were differences in conduction velocity along the length of the excitation wave. The implications of the analysis are considerable, since the gratifying agreement between the theoretical and measured results indicates that the details of the extracellular waveforms can be explained on the basis of the distribution of intracellular currents; i.e., extracellular potentials provide a sensitive index of intracellular current flow.

Action Potentials↗

Effects of l-carnitine on action potential of canine papillary muscle during hypoxic perfusion.

Under hypoxic (95% N2 + 5% CO2) perfusion, electrophysiological effects of L-carnitine on canine papillary muscles were studied using standard microelectrode techniques. During hypoxic perfusion for 60 min, resting membrane potential (RMP), action potential amplitude (APA) and maximum upstroke velocity of phase 0 were decreased, and action potential duration (APD) and effective refractory period (ERP) were shortened. Application of L-carnitine 25 mM under hypoxic perfusion increased RMP and APA and prolonged APD and ERP significantly. As effects of L-carnitine during hypoxic perfusion might be that of hypertonicity, effects of sucrose of the same tonicity as L-carnitine were studied under hypoxia. Sucrose did not cause significant changes on various parameters of action potential compared with hypoxic perfusion. It was suggested that the increase in RMP, and the prolongation of APD and ERP might be caused by an increase in intracellular ATP content. The findings in this study could be an explanation of possible antiarrhythmic effects of L-carnitine.

Action Potentials↗

After-hyperpolarization and receptor potential attenuation following bursts of action potentials in an insect mechanoreceptor.

The receptor potential in the sensory neuron of the cockroach femoral tactile spine was recently observed by raising the axon into an oil bath and measuring the decrementally conducted receptor current. Although action potential discharge in this receptor adapts rapidly, there was no evidence of adaptation in the receptor potential. In the present work we report that bursts of action potentials in the neuron produce a prolonged after-hyperpolarization and attenuate the receptor potential. Both of these effects could be important in receptor adaptation and we sought to identify their origin. It was impossible to control ionic concentrations in the fluid surrounding the sensory neuron because of an effective glial barrier, but it was possible to infuse the tissues with chemical agents which are known to block ionic membrane processes. Cobalt and cadmium, which inhibit calcium influx, eliminated the effects of action potentials, and ouabain had similar effects. These results suggest that both a calcium-activated potassium conductance and an electrogenic sodium pump are involved in these phenomena. However, it is argued that the former is probably more important.

Action Potentials↗

Latency and amplitude tuning curves of the N1 and N2 components of the cochlear nerve compound action potential.

Compound action potential tuning curves (CAP TCs) generated by masking the N1 component of the CAP provide a means of assessing the ability of the cochlea to selectively tune to certain stimuli. This paper examines some of the factors which can influence this TC when a moderately intense (i.e. 40-80 dB SPL) probe stimulus is used. At these levels, each of the four corners of the trapezoidal stimulus envelope is capable of generating a CAP. Also, short stimulus rise times can merge the CAPs produced by the first two corners, but this does not appear to have a major effect on the CAP TC. It was shown that the N2 component of the CAP for the first corner of the stimulus is equally capable of producing a well-tuned TC. Another study has shown that, in addition to amplitude decrements, one can use latency increases as a criterion for CAP TCs. We have demonstrated that latency TCs are more finely tuned than amplitude TCs at high levels, especially when the stimulus rise time is short.

Animals↗

Satellite potentials of motor unit action potentials in normal muscles: a new hypothesis for their origin.

OBJECTIVE: A satellite potential is a late component of the motor unit action potential (MUAP) that occurs both in pathologic and normal muscle. We investigated the physiological mechanisms responsible for satellite potentials in normal muscle by relating the latencies of MUAP features to the timing of the underlying electrical events. METHODS: We analyzed 21 MUAPs with satellite potentials that had been recorded using a monopolar needle electrode from brachial biceps and tibialis anterior muscles in 10 normal subjects. We estimated the endplate-to-electrode, endplate-to-tendon, and satellite propagation times from the latencies, with respect to the MUAP onset, of the MUAP spike, terminal wave, and satellite. RESULTS: Satellite latencies ranged from 8.8 to 32 ms, too long to be explained by mechanisms involving regenerating axons or atrophic muscle fibers. The spike-to-satellite time intervals approximated either twice the spike-to-terminal-wave interval (17 MUAPs) or twice the terminal-wave latency (4 MUAPs). CONCLUSIONS: These results are consistent with the hypothesis that satellite potentials are due to retrograde propagation in a non-innervated muscle fiber that is connected with an innervated muscle fiber at one of the muscle/tendon junctions. Such a configuration could arise as a result of longitudinal muscle-fiber splitting.

Action Potentials↗

K+-induced twitch potentiation is not due to longer action potential.

The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.

Action Potentials↗

Forward masking and unmasking of the offset cochlear compound action potential of the gerbil: comparison with suppression areas of the onset cochlear compound action potential.

Simultaneous and forward maskers were used to generate 'onset' and 'offset' compound action potential tuning curves (TCs) in the gerbil. The simultaneously masked offset TC, generated in response to a 16 kHz, 65 dB SPL probe stimulus, is W-shaped, with a low frequency tip at 11 kHz, a high frequency tip at 20 kHz, and a peak which occurs at 16 kHz. The 16 kHz forward masked onset TC has a single tip which occurs at 11 kHz. Although it lacks the finely tuned peak and high frequency tip of the stimultaneously masked offset TC, its single tip is more finely tuned than the low frequency tip of the simultaneously masked offset TC. Normalizing these two TCs [(1977) J. Acoust. Soc. Am. 62, 1048-1051] produces a figure which resembles 11 kHz onset TCs with their nonoverlapping regions which are analogs of two-tone suppression (2TS). A similar pattern occurs when probe stimuli at frequencies from 13 to 24 kHz are used to generate offset TCs; i.e., the forward masked offset TC resembles an onset TC and normalizing it to a simultaneously masked offset TC produces areas which resemble analogs of 2TS. Unmasking of the forward masked onset TCs [(1979) Hear, Res. 1, 133-154] produces regions of 2TS which are very similar to those produced by unmasking the forward masked offset TC which is generated by a higher frequency tone. These regions of 2TS for the Offset TC, as determined by unmasking, are very similar to the analogs of 2TS described above.

Acoustic Stimulation↗

Teaching field potentials: a microcomputer simulation of the nerve action potential in a bidimensional conductor.

A computer simulation of the extracellular field potential recording of nerve activity is presented. An experimental setup composed of an oscilloscope, a nerve, a conductive surface, and a recording electrode is graphically simulated. The user may study the influence of the position of the recording electrode and of certain nerve properties (membrane potential, velocity of conduction and action potential duration), on the action potential shape. The different waves which constitute the action potential may be analyzed and their peak values plotted as a function of the independent variable (e.g. electrode distance from the nerve). Three-dimensional plots of a set of action potentials as a function of the independent variable may also be obtained. The stimulation allows the user to study the basic factors which determine the configuration of an extracellularly recorded compound nerve action potential.

Action Potentials↗

Computerized evaluation of drug-induced changes in guinea-pig epicardial monophasic action potentials.

The monophasic action potential (MAP) has been widely used for the study of drug effects on cardiac repolarization in vivo. There is, however, no study of drug-induced effects on MAP depolarization, i.e. effects on MAP Vmax and/or MAP rise-time. For this study, we developed a method in the anesthetized open chest guinea-pig. MAP signals were recorded and subjected to on-line computerized analysis, in which parameters describing both depolarization and repolarization were calculated. With the MAP electrode kept at the same epicardial position the MAP rise-time did not vary with time. If the influences of heart rate were eliminated, the intra- and interindividual variation in the MAP duration was very low. Sotalol significantly and dose-dependently prolonged MAP duration, but did not affect rise-time, whereas tocainide significantly and dose-dependently shortened MAP duration and increased rise-time. The effect of tocainide on rise-time is most likely secondary to a reduction in conduction velocity due to a decrease in Vmax in the single cell action potential. These results suggest that monophasic action potential recordings coupled with an on-line computerized analysis may be used for rapid and simple evaluation of drug effects, both on cardiac depolarization and repolarization.

Action Potentials↗

Metabolic energy cost of action potential velocity.

The action potential of the unmyelinated nerve is metabolically expensive. Using the energetic cost per unit length for the biophysically modeled action potential of the squid giant axon, we analyze this cost and identify one possible optimization. The energetic cost arising from an action potential is divided into three separate components: 1) the depolarization of the rising phase; 2) the hyperpolarization of the falling phase; and 3) the largest component, the overlapping of positive and negative currents, which has no electrical effect. Using both the Hodgkin-Huxley (HH) model and an improved version of the HH model (HHSFL), we investigate the variation of these three components as a function of easily evolvable parameters, axon diameter and ion channel densities. Assuming conduction velocity is well designed for each organism, the energy component associated with the rising phase attains a minimum near the biological values of the diameter and channel densities. This optimization is explained by the membrane capacitance per unit length. The functional capacitance is the sum of the intrinsic membrane capacitance and the gating capacitance associated with the sodium channel, and this capacitance minimizes at nearly the same values of diameter and channel density. Because capacitance is temperature independent and because this result is independent of the assumed velocity, the result generalizes to unmyelinated mammalian axons. That is, channel density is arguably an evolved property that goes hand-in-hand with the evolutionary stability of the sodium channel.

Action Potentials↗

Dynamic model for ventricular junctional conductance during the cardiac action potential.

The ventricular action potential was applied to paired neonatal murine ventricular myocytes in the dual whole cell configuration. During peak action potential voltages >100 mV, junctional conductance (g(j)) declined by 50%. This transjunctional voltage (V(j))-dependent inactivation exhibited two time constants that became progressively faster with increasing V(j). G(j) returned to initial peak values during action potential repolarization and even exceeded peak g(j) values during the final 5% of repolarization. This facilitation of g(j) was observed <30 mV during linearly decreasing V(j) ramps. The same behavior was observed in ensemble averages of individual gap junction channels with unitary conductances of 100 pS or lower. Immunohistochemical fluorescent micrographs and immunoblots detect prominent amounts of connexin (Cx)43 and lesser amounts of Cx40 and Cx45 proteins in cultured ventricular myocytes. The time dependence of the g(j) curves and channel conductances are consistent with the properties of predominantly homomeric Cx43 gap junction channels. A mathematical model depicting two inactivation and two recovery phases accurately predicts the ventricular g(j) curves at different rates of stimulation and repolarization. Functional differences are apparent between ventricular myocytes and Cx43-transfected N2a cell gap junctions that may result from posttranslational modification. These observations suggest that gap junctions may play a role in the development of conduction block and the genesis and propagation of triggered arrhythmias under conditions of slowed conduction (<10 cm/s).

Action Potentials↗

Action potential duration-stabilizing action of taurine in guinea pig ventricular myocytes.

To examine taurine actions on the rate of repolarization of action potentials (AP), L-type Ca2+ (ICa), late outward K+ (Ik) and the inward rectifier currents as affected by the external Ca2+ concentrations ([Ca2+]o), whole-cell voltage-clamp and current-clamp experiments were conducted in guinea pig ventricular myocytes. At a high (3.6 mM) [Ca2+]o, 10 mM taurine suppressed both ICa and IK, shortened AP duration and decelerated the rate (-dV/dt) of terminal repolarization of AP. In contrast, at a low (0.9 mM) [Ca2+]o, taurine intensified both ICa and IK, lengthened AP duration and accelerated -dV/dt. However, at either [Ca2+]o, the resting membrane potential was slightly hyperpolarized, and the inward rectifier, current examined by the ramp-pulse protocol remained unaffected by taurine. Taurine is suggested to maintain a stable AP duration by altering the inward Ca2+ and IK in the opposite directions, depending on [Ca2+]o. The relevance of the stabilizing action of taurine on the AP duration to its reported anti-arrhythmic efficacies is discussed.

Action Potentials↗

Effects of limb perturbation on surface recorded nerve action potentials.

The field action potentials are a convolution of source strength and the propagating-point source responses (PPSRs). Surface-recorded peripheral nerve potentials are strongly influenced by the volume-conductor properties of the limb. In this paper the PPSRs are solved based on finite-element formulation, which allows solutions to forward volume-conductor problems involving curved nerves in arbitrarily shaped, inhomogeneous, anisotropic limbs. Effects of limb perturbation on surface-recorded nerve action potentials are simulated based on circular and elliptic cylinders with a uniform cross-section consisting of multiple inhomogeneous and anisotropic regions (fat, muscles, and bone layers). The simulations show that a simple homogeneous model is adequate only for a very superficial nerve that lies completely in the subcutaneous fat layer. Deeper nerves that lie on or within the muscle require a multiple-layer model that takes both the muscle and the fat into account. The cross section only needs to be modeled accurately between the recording site and the nerve location. A circular limb model is adequate for clinical recordings. However, an accurate knowledge of the nerve path is essential for accurate modeling of the action potentials, in both needle and surface recordings.

Action Potentials↗

Effects of 4-aminoquinoline on action potentials of the frog sinus venosus.

The electrophysiological effects of 4-aminoquinoline (4-AQ), a drug structurally related to 4-aminopyridine, were studied on the sinus venosus of the frog Caudiverbera caudiverbera with standard microelectrode techniques. 4-AQ in concentrations (0.01-1.5 mM) that did not modify membrane resting potential, reversibly depressed pacemaker activity and the rate of diastolic depolarization. These effects were not prevented by atropine. 4-AQ also reduced maximum diastolic potential, whereas action potential amplitude, overshoot and dV/dtmax remained unaffected. Action potential duration was prolonged by 4-AQ in a concentration-related manner by slowing down the repolarization phase. The effects upon repolarization and on diastolic depolarization were abolished by doubling extracellular calcium concentration. They were not suppressed, however, by electrically pacing sinus preparations at the pre-drug frequency. A plausible interpretation of the data is that 4-AQ effects are the consequence of a direct inhibition of potassium conductance at the cell membrane.

Action Potentials↗